Drug Treatment of Ischemic Heart Disease

-Fixed "Stable“, Effort Angina -Variant Angina “Primary Angina” -Unstable Angina -Myocardial Infarction

Categories of Ischemic Heart Disease

ST elevation Vasospasm Single Large vessels

1957 Atypical Angina at rest

Variant (Prinzmetal's)

Primary

ST depression

Atherosclerosis Single or multiple

Small vessels

1768 Typical Angina of effort

Classical Secondary

Comparison between primary & secondary angina

Stunning :( مشدوه, مذهول, مصعوق ) Myocardial stunning is the reversible reduction of function of heart contraction after reperfusion not accounted for by tissue damage or reduced blood flow.

A condition that may happen after reperfusion

-Contraction is triggered by influx of calcium through L-type transmembrane calcium channels. -Calcium combines with calmodulin to form a complex that converts the enzyme myosin light-chain kinase to its active form (MLCK*). -MLCK phosphorylates myosin light chains, thereby initiating the interaction of myosin with actin. -Beta2 agonists (and other substances that increase cAMP) may cause relaxation in smooth muscle by accelerating the inactivation of MLCK and by facilitating the expulsion of calcium from the cell.

Control of smooth muscle contraction

Imbalance of the ratio: O2 Supply (Coronary Blood Flow) O2 Demand (Work of the Heart)

Mechanism of IHD

Drugs

Notes Side Effects Action Drug -Prototype, used for more than 150 years. -Usually administered sublingually. -Can be administered by various routes. -Fast onset of action(1-3minutes, Peaks at 10 minutes). -Short duration (15-30minutes). -Reductase enzyme, in liver, breaks down the drug.

Headache. -Hypotension and tachycardia. -Increased intraocular and intracranial pressures. - Methemo-globinemia. -Tolerance: only for the arteriolar effects. -Withdrawal: in workers in ammunition industry.

-Nonspecific smooth muscle relaxant. -Action is due to release of NO, leading to activation of guanylyl cyclase. -Action not antagonized by any known antagonist. Causes general vasodilation: *Arteriolar dilation: short lived (5-10 min) -Decreases systemic blood pressure (afterload). This can elicit the baroreceptor reflex to cause reflex tachycardia and increased contractility, and might increase MVO2. *Venous dilation: more intense, even with low doses, lasts for 30 minutes. -Decreases venous return (preload) and decreases MVO2.

Organic Nitrates Nitroglycerine (GTN)

-Prevent actions of catecholamines, so more effective during exertion. -Do not dilate coronary arteries, might constrict them. -Do not increase collateral blood flow. -Cause subjective and objective improvement: decreased number of anginal episodes, nitroglycerine consumption, enhanced exercise tolerance, and improved ECG.

Beta Adrenergic Blockers

-Hypotension. -Headache, dizziness. -Flushing. -Peripheral edema. May be dangerous in the presence of heart failure and in patients susceptible to hypotension.

-Particularly beneficial in vasospasm. -Can also affect platelets aggregation.

Calcium Channel Blockers

-Inhibits the uptake of adenosine and inhibits adenosine deaminase enzyme. -Thought to be a good coronary dilator. -Increases the blood flow to the normal area i.e. “Coronary Steal Phenomenon”. -Still used as an antiplatelet drug (in TIAs), but not better than aspirin.

Dipyridamole

Others: -ACEI. -Anticoagulants and/or Thrombolytic Therapy. -Cholesterol Lowering Agents. -Angioplasty -Surgery.

Newer Antianginal Drugs -Metabolic modulators: Ranolazine. -Direct bradycardic agents: Ivabradine. -Potassium channel activators: Nicorandil. -Rho-kinase inhibitors: Fasudil. -Sulfonylureas: Glibenclamide. -Thiazolidinediones. -Vasopeptidase inhibitors. -Nitric oxide donors: L- arginine. -Capsaicin. -Amiloride.

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Drugs Site of Action

Organic Nitrates

Calcium Channel Blockers

Drug Combinations